Biophysical properties of voltage-gated Na+ channels in frog parathyroid cells and their modulation by cannabinoids

The membrane properties of isolated frog parathyroid cells were studied using perforated and conventional whole-cell patch-clamp techniques. Frog parathyroid cells displayed transient inward currents in response to depolarizing pulses from a holding potential of -84 mV. We analyzed the biophysical properties of the inward currents. The inward currents disappeared by the replacement of external Na+ with NMDG(+) and were reversibly inhibited by 3 mu mol l(-1) TTX, indicating that the currents occur through the TTX-sensitive voltage-gated Na+ channels. Current density elicited by a voltage step from -84 mV to -24 mV was -80 pA pF(-1) in perforated mode and -55 pA pF(-1) in conventional mode. Current density was decreased to -12 pA pF(-1) by internal GTP gamma S (0.5 mmol l(-1)), but not affected by internal GDP beta S (1 mmol l(-1)). The voltage of half-maximum (V-1/2) activation was -46 mV in both perforated and conventional modes. V-1/2 of inactivation was -80 mV in perforated mode and -86 mV in conventional mode. Internal GTP gamma S (0.5 mmol l(-1)) shifted the V-1/2 for activation to -36 mV and for inactivation to -98 mV. A putative endocannabinoid, 2-arachidonoylglycerol ether (2-AG ether, 50 mu mol l(-1)) and a cannabinomimetic aminoalkylindole, WIN 55,212-2 (10 mu mol l(-1)) also greatly reduced the Na+ current and shifted the V-1/2 for activation and inactivation. The results suggest that the Na+ currents in frog parathyroid cells can be modulated by cannabinoids via a G protein-dependent mechanism.